The overall goal of this R21 proposal is to develop a methodology to increase the resolution of magnetic resonance (MR) metabolite spectra in live mice. Although in vivo MR spectroscopy is increasingly used for biochemical and medical studies, the spectra often suffer from poor resolution, which diminishes seriously their utility. In previous work on excised organs and tissues we have shown that it is possible to increase the spectral resolution significantly by applying the so-called phase-corrected magic angle turning (PHORMAT) technique, where a slow rotation of the sample around an axis making an angle of 54 degrees 44 ' relative to the external magnetic field is combined with special RF pulse sequences. With this method spinning speeds as low as 1 Hz could be employed, which might make it possible to use this technique to study large intact tissues and even live animals. It was found that mice could tolerate spinning in a 2 Tesla magnet with a frequency of at least 8 Hz and for a duration of at least 40 minutes without any apparent problems, illustrating the feasibility of the slow-spinning approach. In this application the viability of the PHORMAT approach for in vivo applications will be explored. To this end the necessary instrumentation will be developed integrating PHORMAT with MR imaging technologies, the PHORMAT technique will be improved to increase its MR sensitivity and reduce its measuring time, and 1H PHORMAT experiments will be carried out on different organs and tissues of live mice using a 2 Tesla small-animal imaging instrument, available at PNNL. The results will be used to determine the impact of motions in the animal on the spectral resolution, to investigate the quantitative character of the spectra, to evaluate the possibilities of the PHORMAT approach in high magnetic fields, and to evaluate the feasibility of PHORMAT using other magnetic nuclei than protons. Ultimately the project might provide a new unique capability for in vivo MR spectroscopy research in animals that will make it possible to analyze MR metabolite spectra in considerably more detail than could be done previously. This would significantly increase the utility of MR spectroscopy for biomedical research, diagnosis, and therapy evaluation in live animals. In fact, the technique may even become useful for examining patients in the clinic, in this case by rotating the magnetic field rather than the patient.